US2007149599A1PendingUtilityA1
Polymorphs of bicifadine hydrochloride
Est. expiryNov 8, 2022(expired)· nominal 20-yr term from priority
A61K 31/40A61P 25/04C07D 209/52A61K 9/20C07B 2200/13A61K 9/48
59
PatentIndex Score
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Cited by
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Claims
Abstract
A new polymorphic crystalline form of bicifadine hydrochloride, designated form B, which is more thermodynamically stable than the previously known polymorphic form of bicifadine hydrochloride, designated as form A, methods for preparing said crystalline form B and pharmaceutical compositions containing said crystalline form B.
Claims
exact text as granted — not AI-modified1 - 23 . (canceled)
24 . A solid composition comprising bicifadine hydrochloride polymorph form B crystals having a distinct infrared profile characterized by one or more of the following infrared spectrum peaks in wavenumbers (cm −1 ):
3185
1111
2769
1022
2437
963
2276
904
2108
891
1908
856
1804
818
1658
783
1596
719
1518
684
1453
660
1403
637
1343
580
1305
532
1274
475
1209
422
1131
and a distinct x-ray powder diffraction (XRPD) profile characterized by one or more of the following XRPD peaks expressed in terms of “d” spacings and relative intensities I (s=strong, m=medium, w=weak, v=very, d=diffuse.)
2θ (deg)
D(Å)
I a
5.08
17.39
vs
10.07
8.77
s
15.19
5.83
s
16.83
5.27
s
18.64
4.76
md
18.76
4.73
md
19.64
4.52
w
20.16
4.40
m
21.96
4.05
m
22.37
3.97
s
23.16
3.84
w
24.00
3.70
w
25.27
3.52
d
27.33
3.26
md
27.74
3.21
m
29.00
3.08
m
30.43
2.93
md
31.84
2.80
wd
32.29
2.77
w
35.27
2.54
wd
35.64
2.52
w
a s = strong, m = medium, w = weak, v = very, d = diffuse
25 . The composition of claim 24 , which comprises a tablet.
26 . The composition of claim 24 , which comprises a capsule.
27 . The composition of claim 24 , wherein the composition comprises said polymorph form B in a unit dosage amount of between 25 mg to 600 mg.
28 . The composition of claim 24 , wherein the composition comprises said polymorph form B in a unit dosage amount of between 200 mg to 400 mg.
29 . The composition of claim 24 , wherein said composition comprises said bicifadine hydrochloride polymorph form B in a controlled release formulation.
30 . The composition of claim 29 , wherein said controlled release formulation includes a slow release polymer.
31 . The composition of claim 30 , wherein said slow release polymer comprises hydroxypropyl methylcellulose.
32 . The composition of claim 24 , wherein said composition includes a carrier selected from the group consisting of microcrystalline cellulose, lactose, sucrose, fructose, glucose dextrose, or other sugars, di basic calcium phosphate, calcium sulfate, cellulose, methylcellulose, cellulose derivatives, kaolin, mannitol, lactitol, maltitol, xylitol, sorbitol, sugar alcohols, dry starch, dextrin, maltodextrin, polysaccharides, inositol, and mixtures thereof.
33 . The composition of claim 24 , wherein said composition is in the form of a coated tablet.
34 . A composition comprising bicifadine hydrochloride polymorph form B crystals having a distinct infrared profile characterized by one or more of the following infrared spectrum peaks in wavenumbers (cm −1 ):
3185
1111
2769
1022
2437
963
2276
904
2108
891
1908
856
1804
818
1658
783
1596
719
1518
684
1453
660
1403
637
1343
580
1305
532
1274
475
1209
422
1131
and a distinct x-ray powder diffraction (XRPD) profile characterized by one or more of the following XRPD peaks expressed in terms of “d” spacings and relative intensities I (s=strong, m=medium, w=weak, v=very, d=diffuse.)
2θ (deg)
D(Å)
I a
5.08
17.39
vs
10.07
8.77
s
15.19
5.83
s
16.83
5.27
s
18.64
4.76
md
18.76
4.73
md
19.64
4.52
w
20.16
4.40
m
21.96
4.05
m
22.37
3.97
s
23.16
3.84
w
24.00
3.70
w
25.27
3.52
d
27.33
3.26
md
27.74
3.21
m
29.00
3.08
m
30.43
2.93
md
31.84
2.80
wd
32.29
2.77
w
35.27
2.54
wd
35.64
2.52
w
a s = strong, m = medium, w = weak, v = very, d = diffuse,
said composition prepared by a method comprising, providing a slurry of bicifadine hydrochloride in an organic solvent having a boiling point of at least about 50° C., heating said slurry to a temperature at which said slurry is a clear solution, allowing said solution to cool to a temperature of at most about 35° C., and maintaining said cooled solution at said temperature of at most about 35° C. for a period of time sufficient to allow said polymorph form B to crystallize out in the form of crystals from said solution.
35 . The composition of claim 34 , wherein said cooling is carried out while said solution is agitated.
36 . The composition of claim 34 , wherein said cooled solution is maintained at a temperature of at most 35° C. while subjected to agitation.
37 . The composition of claim 34 , wherein said heated solution is allowed to cool to a temperature of from about −200° C. to 0° C.
38 . A composition comprising bicifadine hydrochloride polymorph form B crystals having a distinct infrared profile characterized by one or more of the following infrared spectrum peaks in wavenumbers (cm −1 ):
3185
1111
2769
1022
2437
963
2276
904
2108
891
1908
856
1804
818
1658
783
1596
719
1518
684
1453
660
1403
637
1343
580
1305
532
1274
475
1209
422
1131
and a distinct x-ray powder diffraction (XRPD) profile characterized by one or more of the following XRPD peaks expressed in terms of “d” spacings and relative intensities I (s=strong, m=medium, w=weak, v=very, d=diffuse.)
2θ (deg)
D(Å)
I a
5.08
17.39
vs
10.07
8.77
s
15.19
5.83
s
16.83
5.27
s
18.64
4.76
md
18.76
4.73
md
19.64
4.52
w
20.16
4.40
m
21.96
4.05
m
22.37
3.97
s
23.16
3.84
w
24.00
3.70
w
25.27
3.52
d
27.33
3.26
md
27.74
3.21
m
29.00
3.08
m
30.43
2.93
md
31.84
2.80
wd
32.29
2.77
w
35.27
2.54
wd
35.64
2.52
w
a s = strong, m = medium, w = weak, v = very, d = diffuse,
said composition prepared by a method comprising, providing solid polymorph form A crystals of bicifadine hydrochloride, agitating said crystals at a temperature of from about −200° C. to about 50° C. to convert said polymorph form A crystals to said polymorph form B crystals.
39 . The composition of claim 38 , wherein said agitation is carried out by grinding.
40 . The compostion of claim 38 , wherein said agitation is carried out at a temperature of from about −200° C. to about 35° C.
41 . The composition of claim 40 wherein said agitation is carried out at a temperature of about −200° C. to about 0° C.
42 . A composition comprising bicifadine hydrochloride polymorph form B crystals having a distinct infrared profile characterized by one or more of the following infrared spectrum peaks in wavenumbers (cm −1 ):
3185
1111
2769
1022
2437
963
2276
904
2108
891
1908
856
1804
818
1658
783
1596
719
1518
684
1453
660
1403
637
1343
580
1305
532
1274
475
1209
422
1131
and a distinct x-ray powder diffraction (XRPD) profile characterized by one or more of the following XRPD peaks expressed in terms of “d” spacings and relative intensities I (s=strong, m=medium, w=weak, v=very, d=diffuse.)
2θ (deg)
D(Å)
I a
5.08
17.39
vs
10.07
8.77
s
15.19
5.83
s
16.83
5.27
s
18.64
4.76
md
18.76
4.73
md
19.64
4.52
w
20.16
4.40
m
21.96
4.05
m
22.37
3.97
s
23.16
3.84
w
24.00
3.70
w
25.27
3.52
d
27.33
3.26
md
27.74
3.21
m
29.00
3.08
m
30.43
2.93
md
31.84
2.80
wd
32.29
2.77
w
35.27
2.54
wd
35.64
2.52
w
s = strong, m = medium, w = weak, v = very, d = diffuse,
said composition prepared by a method comprising adding bicifadine hydrochloride in either polymorph form A or a mixture of polymorph from A and polymorph form B to an organic solvent to form a slurry and applying kinetic energy to said slurry at a temperature of at most of about 35° C. or for at least a period of time sufficient to form said polymorph form B crystals of bicifadine hydrochloride.
43 . The composition of claim 42 , wherein said kinetic energy is applied by agitation.
44 . The composition of claim 42 , wherein said kinetic energy is applied by stirring.Join the waitlist — get patent alerts
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